HIV status, breastfeeding modality at 5 months and postpartum maternal weight changes over 24 months in rural South Africa

ObjectiveTo determine the effect of infant feeding practices on postpartum weight change among HIV-infected and -uninfected women in South Africa.MethodsIn a non-randomised intervention cohort study of antiretroviral therapy-naïve women in South Africa, infants were classified as exclusive (EBF), mixed (MF) or non-breastfed (NBF) at each visit. We analysed infant feeding cumulatively from birth to 5 months using 24-hour feeding history (collected weekly for each of the preceding 7 days). Using generalised estimating equation mixed models, allowing for repeated measures, we compared postpartum weight change (kg) from the first maternal postpartum weight within the first 6 weeks (baseline weight) to each subsequent visit through 24 months among 2340 HIV-infected and -uninfected women with live births and at least two postpartum weight measurements.ResultsHIV-infected (?0.2 kg CI: ?1.7 to 1.3 kg; P = 0.81) and -uninfected women (?0.5 kg; 95% CI: ?2.1 to 1.2 kg; P = 0.58) had marginal non-significant weight loss from baseline to 24 months postpartum. Adjusting for HIV status, socio-demographic, pregnancy-related and infant factors, 5-month feeding modality was not significantly associated with postpartum weight change: weight change by 24 months postpartum, compared to the change in the reference EBF group, was 0.03 kg in NBF (95% CI: ?2.5 to +2.5 kg; P = 0.90) and 0.1 kg in MF (95% CI: ?3.0 to +3.2 kg; P = 0.78).ConclusionHIV-infected and -uninfected women experienced similar weight loss over 24 months. Weight change postpartum was not associated with 5-month breastfeeding modality among HIV-infected and -uninfected women.ObjectifDéterminer l'effet des pratiques d'alimentation des nourrissons sur la variation du poids postpartum chez les femmes infectées et non infectées par le VIH en Afrique du Sud.MéthodesDans une étude de cohorte d'intervention non randomisée sur la thérapie aux antirétroviraux, les nourrissons de femmes naïves pour le traitement en Afrique du Sud, ont été classés comme allaités exclusivement au sein (EBF), recevant une alimentation mixte (MF) ou non allaités au sein (NBF), à chaque visite. Nous avons analysé l'alimentation du nourrisson cumulativement de la naissance à cinq mois, en utilisant l'historique de l'alimentation sur 24 heures (recueillies hebdomadairement pour chacun des sept jours précédents). En utilisant l’équation d'estimation des modèles mixtes généralisés, permettant des mesures répétées, nous avons comparé les changements de poids (kg) postpartum de la première mesure du poids postpartum de la mère endéans les six premières semaines (poids de base) au poids à chaque visite subséquente durant 24 mois chez 2340 femmes infectées et non infectées par le VIH, ayant eu des naissances vivantes et au moins deux mesures du poids postpartum.RésultatsLa perte de poids des femmes infectées (-0,2 kg; IC: -1,7 à 1,3 kg; P = 0,81) et non infectées (0,5 kg, IC95%: -2,1 à 1,2 kg; P = 0,58) par le VIH était marginalement non significative de la base à 24 mois postpartum. En ajustant pour le statut VIH et sociodémographique, pour les facteurs liés à la grossesse et infantiles, le mode d'alimentation sur cinq mois n’étaient pas significativement associé à la variation du poids postpartum; la variation de poids sur 24 mois postpartum comparée à celle dans le groupe EBF de référence, était de 0,03 kg chez les NBF (IC95%: -2,5 à 2,5 kg; P = 0,90) et 0,1 kg chez les MF (IC95%: -3,0 à 3,2 kg; P = 0,78).ConclusionLes femmes infectées et non infectées par le VIH connaissent une perte de poids similaire sur 24 mois. La variation du poids postpartum n'a pas été associée au mode d'allaitement à cinq mois chez les femmes infectées et non infectées par le VIH.ObjetivoDeterminar el efecto de las prácticas de alimentación de los bebés en la variación del peso materno postparto entre mujeres infectadas y no infectadas con VIH en Sudáfrica.MétodosEn una intervención en Sudáfrica no aleatorizada, dentro de un estudio de cohortes de mujeres que no habían recibido anteriormente terapia antirretroviral (naive) – los bebés de se clasificaron como recibiendo exclusivamente el pecho (EP), alimentación mixta (AM), o que no eran amamantados (NA) en cada visita. Hemos analizado la alimentación acumulativa del bebé, desde el nacimiento hasta los cinco meses de edad, utilizando un historial de alimentación de 24 horas (recogido semanalmente para los 7 días anteriores). Utilizando modelos mixtos de ecuaciones de estimación generalizadas, permitiendo medidas repetidas, hemos comparado el cambio de peso (kg) durante el postparto - desde la primera pesada dentro de las primeras seis semanas postparto (peso inicial) con cada visita subsiguiente, durante los 24 meses posteriores, para 2340 mujeres - infectadas con VIH y sin infectar – que dieron a luz bebés nacidos vivos y que tenían recogidas al menos dos pesadas postparto.ResultadosLas mujeres infectadas con VIH (-0.2 kg IC: -1.7 – 1.3 kg; P = 0.81) y aquellas no infectadas (-0.5kg; 95% IC: -2.1 – 1.2 kg; P =0.58) tenían una pérdida de peso marginal y no significativa entre el comienzo del estudio hasta los 24 meses después del parto. Ajustando para el estatus de VIH, los factores sociodemográficos y relacionados con el embarazo y el bebé, la modalidad de alimentación del bebé durante sus cinco primeros meses no estaba significativamente asociada con el cambio de peso postparto: el cambio de peso 24 meses después del parto, comparada con el cambio en referencia al grupo EP, era de 0.03 kg en NA (IC 95%: -2.5 – +2.5 kg; P = 0.90) y 0.1 kg en AM (IC 95%: -3.0 – +3.2 kg; P = 0.78).ConclusiónLas mujeres infectadas con VIH y aquellas sin infección experimentaron una pérdida de peso similar en los 24 meses postparto. El cambio de peso no estaba asociado con la modalidad de amamantamiento entre las mujeres VIH positivas y VIH negativas

The influence of passive wedge-wire screen aperture and flow velocity on juvenile European eel exclusion, impingement and passage

The European eel (Anguilla anguilla) is a critically endangered catadromous fish. The decline has partly been attributed to water management infrastructure that abstract water from rivers for potable and industrial water supply, irrigation, hydroelectric power generation and flood defence; eels can be impinged on weedscreens and trashracks and entrained in pumps and turbines. The Eel Regulations (England and Wales) 2009 stipulates measures are required to provide safe (upstream and downstream) passage of eels past such hazardous intakes. Preventing impingement and entrainment of upstream migrating (glass eel and elver) and river-resident (yellow) juvenile eels at hazardous intakes may require fine-mesh aperture screens and low approach velocities due to eels' small size and relatively poor swimming capacity but quantitative evidence is lacking. Here, passive wedge-wire screen aperture (1, 2, 3 and 5 mm) and depth-averaged flow velocities (0, 0.1, 0.15 and 0.2 m∙s−1) both influenced the fate (i.e., impingement or passage) and behaviour (i.e., migratory separation or behavioural avoidance) of two size classes of juvenile eels (60–80 mm glass eels and 100–160 mm elvers) in an experimental flume. One and 2 mm aperture screens were required to physically exclude 60–80 mm and 100–160 mm. Up to 90% and 100% of the 60–80 mm and 100–160-mm size class eels were impinged at 0.2 m∙s−1 depth-averaged flow velocity, which also positively influence number of screen contacts per eel and time to eel fate (from first contact). A small proportion of 60–80 mm eels (9.2%) did not approach the screen due to migratory separation (i.e., positive rheotaxis) and eels narrower than the screen aperture did not always pass through the screen, and thus other biological or hydraulic processes may also influence screen passage. It is hoped that these findings help improve screening guidance for regulators, key stakeholders and water abstraction managers to further improve protective measures required for critically endangered eels

Impact of Antiretroviral Therapy on Incidence of Pregnancy among HIV-Infected Women in Sub-Saharan Africa: A Cohort Study

A multicountry cohort study in sub-Saharan Africa by Landon Myer and colleagues reveals higher pregnancy rates in HIV-infected women on antiretroviral therapy (ART)

Analysis of Xq27-28 linkage in the international consortium for prostate cancer genetics (ICPCG) families.

BACKGROUND: Genetic variants are likely to contribute to a portion of prostate cancer risk. Full elucidation of the genetic etiology of prostate cancer is difficult because of incomplete penetrance and genetic and phenotypic heterogeneity. Current evidence suggests that genetic linkage to prostate cancer has been found on several chromosomes including the X; however, identification of causative genes has been elusive. METHODS: Parametric and non-parametric linkage analyses were performed using 26 microsatellite markers in each of 11 groups of multiple-case prostate cancer families from the International Consortium for Prostate Cancer Genetics (ICPCG). Meta-analyses of the resultant family-specific linkage statistics across the entire 1,323 families and in several predefined subsets were then performed. RESULTS: Meta-analyses of linkage statistics resulted in a maximum parametric heterogeneity lod score (HLOD) of 1.28, and an allele-sharing lod score (LOD) of 2.0 in favor of linkage to Xq27-q28 at 138 cM. In subset analyses, families with average age at onset less than 65 years exhibited a maximum HLOD of 1.8 (at 138 cM) versus a maximum regional HLOD of only 0.32 in families with average age at onset of 65 years or older. Surprisingly, the subset of families with only 2-3 affected men and some evidence of male-to-male transmission of prostate cancer gave the strongest evidence of linkage to the region (HLOD = 3.24, 134 cM). For this subset, the HLOD was slightly increased (HLOD = 3.47 at 134 cM) when families used in the original published report of linkage to Xq27-28 were excluded. CONCLUSIONS: Although there was not strong support for linkage to the Xq27-28 region in the complete set of families, the subset of families with earlier age at onset exhibited more evidence of linkage than families with later onset of disease. A subset of families with 2-3 affected individuals and with some evidence of male to male disease transmission showed stronger linkage signals. Our results suggest that the genetic basis for prostate cancer in our families is much more complex than a single susceptibility locus on the X chromosome, and that future explorations of the Xq27-28 region should focus on the subset of families identified here with the strongest evidence of linkage to this region.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Adverse Drug Reactions in Children—A Systematic Review

Adverse drug reactions in children are an important public health problem. We have undertaken a systematic review of observational studies in children in three settings: causing admission to hospital, occurring during hospital stay and occurring in the community. We were particularly interested in understanding how ADRs might be better detected, assessed and avoided

Comparing two service delivery models for the prevention of mother-to-child transmission (PMTCT) of HIV during transition from single-dose nevirapine to multi-drug antiretroviral regimens

<p>Abstract</p> <p>Background</p> <p>Mother-to-child transmission (MTCT) of HIV has been eliminated from the developed world with the introduction of multi-drug antiretroviral (md-ARV) regimens for the prevention of MTCT (PMTCT); but remains the major cause of HIV infection among sub-Saharan African children. This study compares two service delivery models of PMTCT interventions and documents the lessons learned and the challenges encountered during the transition from single-dose nevirapine (sd-nvp) to md-ARV regimens in a resource-limited setting.</p> <p>Methods</p> <p>Program data collected from 32 clinical sites was used to describe trends and compare the performance (uptake of HIV testing, CD4 screening and ARV regimens initiated during pregnancy) of sites providing PMTCT as a stand-alone service (<it>stand-alone site</it>) versus sites providing PMTCT as well as antiretroviral therapy (ART) (<it>full package site</it>). CD4 cell count screening, enrolment into ART services and the initiation of md-ARV regimens during pregnancy, including dual (zidovudine [AZT] +sd-nvp) prophylaxis and highly active antiretroviral therapy (HAART) were analysed.</p> <p>Results</p> <p>From July 2006 to December 2008, 1,622 pregnant women tested HIV positive (HIV+) during antenatal care (ANC). CD4 cell count screening during pregnancy increased from 60% to 70%, and the initiation of md-ARV regimens increased from 35.5% to 97% during this period. In 2008, women attending ANC at <it>full package </it>sites were 30% more likely to undergo CD4 cell count assessment during pregnancy than women attending <it>stand-alone </it>sites (relative risk (RR) = 1.3; 95% confidence interval (CI): 1.1-1.4). Enrolment of HIV+ pregnant women in ART services was almost twice as likely at <it>full package </it>sites than at <it>stand-alone </it>sites (RR = 1.9; 95% CI: 1.5-2.3). However, no significant differences were detected between the two models of care in providing md-ARV (RR = 0.9; 95% CI: 0.9-1.0).</p> <p>Conclusions</p> <p>All sites successfully transitioned from sd-nvp to md-ARV regimens for PMTCT. <it>Full package </it>sites offer the most efficient model for providing immunological assessment and enrolment into care and treatment of HIV+ pregnant women. Strengthening the capacity of <it>stand-alone </it>PMTCT sites to achieve the same objectives is paramount.</p

Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction.

Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Uganda's experience in Ebola virus disease outbreak preparedness, 2018-2019.

BACKGROUND: Since the declaration of the 10th Ebola Virus Disease (EVD) outbreak in DRC on 1st Aug 2018, several neighboring countries have been developing and implementing preparedness efforts to prevent EVD cross-border transmission to enable timely detection, investigation, and response in the event of a confirmed EVD outbreak in the country. We describe Uganda's experience in EVD preparedness. RESULTS: On 4 August 2018, the Uganda Ministry of Health (MoH) activated the Public Health Emergency Operations Centre (PHEOC) and the National Task Force (NTF) for public health emergencies to plan, guide, and coordinate EVD preparedness in the country. The NTF selected an Incident Management Team (IMT), constituting a National Rapid Response Team (NRRT) that supported activation of the District Task Forces (DTFs) and District Rapid Response Teams (DRRTs) that jointly assessed levels of preparedness in 30 designated high-risk districts representing category 1 (20 districts) and category 2 (10 districts). The MoH, with technical guidance from the World Health Organisation (WHO), led EVD preparedness activities and worked together with other ministries and partner organisations to enhance community-based surveillance systems, develop and disseminate risk communication messages, engage communities, reinforce EVD screening and infection prevention measures at Points of Entry (PoEs) and in high-risk health facilities, construct and equip EVD isolation and treatment units, and establish coordination and procurement mechanisms. CONCLUSION: As of 31 May 2019, there was no confirmed case of EVD as Uganda has continued to make significant and verifiable progress in EVD preparedness. There is a need to sustain these efforts, not only in EVD preparedness but also across the entire spectrum of a multi-hazard framework. These efforts strengthen country capacity and compel the country to avail resources for preparedness and management of incidents at the source while effectively cutting costs of using a "fire-fighting" approach during public health emergencies

Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants

Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Peer reviewe